The present invention relates to an apparatus and system for observing a biological sample, and a method therefor.
With the advent of the CCD (charge coupled device), solid-state area image sensor elements have been developed greatly and the characteristics of the solid-state area image sensor elements have considerably improved. Although a solid-state area image sensor element is slightly inferior to a conventional camera tube in terms of resolution, it requires no optical system for forming an image. In addition, the function of photoelectric conversion of a large number of pixels, storage function, and charge read-out function of the solid-state area image sensor element are integrated into an LSI as a solid-state area image sensor device. Therefore, the solid-state area image sensor element is superior to the camera tube in terms of ease in handling, prevention of sticking caused by intense light and of image distortion, and the like. Owing to such advantages, camera tubes have recently been replaced with solid-state area image sensor elements in the field of broadcasting and the like.
Observation of minute biological samples such as cultured cells is mainly performed by a transmission type microscope. Especially for observation of a sample dipped in a liquid such as a culture medium, an inverted microscope having an objective lens arranged below the sample is used. When a microscopic image is recorded, a camera or a video camera mounted on the microscope is used. In addition, especially in the observation of a cultured cell, if the temperature, humidity, and carbon dioxide concentration of the sample must be kept constant, a heat insulating unit, a humidifier, a carbonic acid gas supply unit, and the like are mounted on the sample table of the microscope.
An example of observation of a biological sample by means of a solid-state area image sensor element is disclosed in Japanese Patent Laid-Open No. 2-208541. The disclosed apparatus is designed to detect an immunologic agglutination reaction. In the apparatus, a light-emitting diode is mounted on an agglutination reaction inspection plate, and a light-shielding mask, a condenser lens, and a one-dimensional CCD sensor are arranged below the plate in this order.
A microscope is an optical system including several lenses, prisms, mirrors, and the like. The size of this instrument including optical paths for forming images is considerably large. The size of the instrument is further increased if it includes a video camera required for recording images, and units for keeping the environment of a sample constant, e.g., a heat insulating unit, a humidifier, and a carbonic acid gas supply unit.
Furthermore, since a microscope is a high-precision instrument, it demands careful handling. Therefore, once, for example, the optical axis is shifted, special skills are needed to adjust the optical axis.
Moreover, in general, the heat insulating unit, the humidifier, the carbonic acid gas supply unit, and the like mounted on the sample table of the microscope easily cause variations in conditions such as a variation in temperature as compared with an incubator for performing normal cell cultivation. Since it is difficult to reproduce the same environment as that of the incubator on the sample table, accurate observation is difficult to perform.
In a conventional biological sample observation apparatus using a solid-state area image sensor element, since an optical system including several lenses is arranged between a sample and the image sensor element, problems similar to those in the microscope are posed, i.e., the size of the apparatus is increased, careful handling and adjustment for forming images are demanded, and the like.